Gastric Carcinoma In The Western Region Of Nepal Biology Essay

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Gastric cancer is among the most common malignancies in Asia, comprising 74% of all global cases. Identifying the environmental risk factors may possibly shed more light on effective treatment and the prevention of this disease. The aim of our study is to document different histologic types of gastric cancer as per age, sex and ethnic groups in the patients in Nepal, to know the frequency of different gross and microscopic subtypes (according to Lauren's classification) of tumor, to find out the association of H. pylori and other major risk factors with gastric cancer.

Materials and Methods

The present study is a hospital based retrospective study done in the Department of Pathology, Manipal Teaching Hospital, Pokhara, Nepal, from Jan 1999 to July 2010. All the endoscopic biopsies and gastrectomy specimens from patients with diagnosed gastric carcinoma were reviewed and the clinical and other data were analyzed.

Results

In this study period, a total of 1223 cases related to stomach were received in Department of Pathology. Considering the inclusion and exclusion criteria, a total of 397 cases - 315 cases of endoscopic biopsy and 82 cases of gastrectomy - were included in the study. Among all cases in Gurung, Chhetri and Brahmin communities, we retrieved data regarding risk factors in 93, 65 and 50 cases respectively. Significant relationship was found between the three risk factors studied and the ethnic groups. Smoked meat and alcohol were found to be associated with gastric carcinoma more in Gurungs and Chhetris than in Brahmins (p= 0.0001). On the contrary, cases among Brahmins are found to more associated with smoking than Gurungs and Chhetris (p= 0.0001).

Conclusion

Gastric carcinoma is a common malignancy in this part of world and most high risk group includes elderly males with history of alcoholism & smoked meat from Gurung community and with history of smoking from Brahmin family. We advise that regular endoscopic surveillance should be done at least in high risk group for the early detection of cancer.

Key Words

Gastric Carcinoma, Ethnicity, Nepal

Background

Gastrointestinal cancers account for a large fraction of human neoplasms. They are almost without exception incurable when gross metastases exist1. Gastric carcinoma is a worldwide disease. In 1990, it was the second most common cancer in the world with an estimated 800,000 new cases every year, 60% of them being in developing countries2. The areas of highest incidence include Eastern Asia, South America and Eastern Europe and those of lower incidence include North America, North Europe, most parts of Africa and South Eastern Asia3, 4. However, there has been a steady decline in its incidence and mortality in past several decades3. Its incidence has markedly decreased in developed countries but remains high in countries like Japan and Chile; Japan having the highest incidence worldwide3,5. In 2008, it has come down to become the 6th cancer worldwide (Age Standardized Rate (ASR) = 14.1%) with an estimated 1,000,000 cases6. Globally it is the 4th commonest cancer in males and 5th in females. Interestingly, 74% of all global cases are from Asia, where gastric carcinoma is the 3 rd commonest cancer (ASR 18.5%) including both genders, the 2nd commonest cancer in males and the 4 th in females6.

The exact cancer prevalence rate in Nepal is unknown due to the lack of a population based national cancer registry. However, every year at least 17,000 new cancer cases are estimated and the figure is expected to go up considerably in the future7. According to the present data from Nepal, it is the 5th common cancer (ASR 8.2%) including both genders, 3rd in males and 6th in females6.

A hospital based study done in Nepal showed that 8.8% were GIT malignancies among the all cancers treated by radiotherapy in Pokhara8. Endoscopic biopsy is widely regarded as the most sensitive and specific diagnostic tool for gastric cancer3. Neoplasms of the various parts of the gastrointestinal tract have a marked variation of distribution. These variations are according to the race, gender, age, the part of the gastrointestinal tract affected, geographical region of the world and other exogenous risk factors9,10. Identifying the environmental risk factors may possibly shed more light on effective treatment and the prevention of these diseases. The aim of our study was to document different histologic types of gastric cancer as per age, sex and ethnic groups in the patients, to know the frequency of different gross and microscopic subtypes (according to Lauren's classification ) of tumor, to find out the association of H. pylori and other major risk factors with gastric cancer.

Materials and Methods

The present study is a hospital based retrospective study done in the Department of Pathology, Manipal Teaching Hospital, Pokhara, Nepal in a period from Jan 1999 to July 2010. All the endoscopic biopsies and gastrectomy specimens in patients with diagnosed gastric carcinoma were reviewed and analyzed. Patients' data were retrieved from the records of the Department of Pathology and also Department of Medical Records, Manipal Teaching Hospital. The parameters analyzed were age, gender, ethnicity, risk factors, gross and microscopic types. For gross morphological types, Borrmann classification was followed (Fig 1). All biopsy tissues were fixed in 10% formalin, processed routinely and stained in Hematoxylin & Eosin and Giemsa stain for H pylori.

Cases excluded from the study were (a) tumors with extensive areas of necrosis and no viable or normal looking tissues (b) cases where the site of biopsy is unclear, not mentioned by endoscopist or could not be identified histologically (c) other types of gastric malignancies ( e.g., lymphoma , gastrointestinal stromal tumor etc ).

The data collected was analyzed using Excel 2003, R 2.8.0 Statistical Package for the Social Sciences (SPSS) for Windows Version 16.0 (SPSS Inc; Chicago, IL, USA) and EPI Info 3.5.1 Windows Version. Chi- square test and Z-test was used to compare the significance difference or relationship between two variables. A p-value of <0.05 (two-tailed) was used to establish statistical significance.

Fig 1: Borrmann Classification - schematic representation 3

Results

In this study period, a total number of approximately 25000 biopsies have been received in the Department of Pathology. Among these, there were a total of 1223 cases related to stomach (Table 1). Majority of endoscopic biopsies were found to be nonmalignant while all of gastrectomy specimens were found to be malignant. Considering the inclusion and exclusion criteria, a total of 397 cases, including 315 cases of endoscopic biopsy and 82 cases of gastrectomy were included in the study.

Table 1: Frequency of endoscopic biopsy and gastrectomy cases

Frequency of Cases

Endoscopic biopsy

Gastrectomy specimen

Total

Total cases

1137

86

1223

Malignant cases

340

86

426

Included

in the study

315

82

397

Table 2 shows age wise frequency of all the studied cases. There is a sharp increase in incidence after 50 years of age and highest number is seen in the age group 51-70 years. Males are more commonly affected than females in a M:F ratio of 1.8:1 (Table 3) .

Table 2: Distribution of cases according to age

Age range

Number of cases

Percentage

CI

21-30

5

1.26

(0.16, 2.36)

31-40

9

2.27

(0.8, 3.73)

41-50

19

4.79

(2.67,6.89)

51-60

143

36

(31.3, 40.74)

61-70

188

47.36

(42.44,52.27)

71+

33

8.31

(5.6, 11.03)

Total

397

Table 3: Distribution of cases according to gender

Gender

Number of cases

Percentage

Ratio

pvalue

Male

254

64

1.8

0.001**

Female

143

36

1.0

Total

397

** Statistically significant (p value<0.05)

Among the different castes, Gurungs are much more commonly affected with 32% of all cases (Table 4). They are closely followed by Chhetri and Brahmins comprising 21% and 15% respectively.

Table 4: Distribution of cases according to caste

Caste

Number of cases

Percentage

CI

Gurung

126

32

(27.16, 36.32)

Chhetri

83

21

(16.91, 24.91)

Brahmin

60

15

(11.59, 18.64)

Magar

29

7

(4.75, 9.86)

Newar

28

7

(4.53, 9.57)

Other castes

71

18

(14.11, 21.65)

Total

397

Table 5: Site wise distribution of all cases included in the study

Site

Number of cases

Percentage

CI

Antrum

277

70

(65.26, 74.29)

Corpus

78

20

(15.74, 23.56)

Fundus

28

7

(4.53, 9.57)

Cardia

14

3

(1.71, 5.34)

Total

397

Antrum was found to be the site of carcinoma in 70% cases, thus being the most common site (Table 5). Gross morphologic types were studies in all 82 gastrectomy cases (Table 6) according to Borrmann's type. Type IV was the commonest type with 33 cases (40% of all 82 cases). Microscopically, all cases were divided as per Lauren's classification and it was found that 210 cases (53%) were of intestinal type (Table 7).

Table 6: Gross morphological distribution of all gastrectomy cases

Bormann's gross types

Description

Num-ber of cases

%

CI

Type

I

Polypoid protruding growth.

0

--

--

Type

II

Fungating growth. with discrete sharply defined borders

22

27

(17.24, 36.42)

Type III

Ulcerated and infiltrating with no discrete borders in ulcer

27

33

(22.76, 43.10)

Type IV

Diffuse infiltrating,

linitis plastica

33

40

(29.63, 50.86)

Total

82

Table 7: Microscopic types - distribution of all cases included in the study

Microscopic types ( Lauren's classification )

Number of cases

Percentage

(n = 82)

CI

Intestinal

210

53

(47.99, 57.81)

Diffuse

123

31

(26.43, 35.53)

Mixed type

64

16

(12.50, 19.74)

Total

397

Associated H.pylori was seen in 32 cases i.e., 8% of all carcinoma cases. (Table 8).

Table 8: Association of H pylori and its relation to site of carcinoma

H. Pylori association with cancer (N = 32, 8% of total cases)

Site of carcinoma

Number of cases

Percentage

CI

Antrum

20

62.5

(45.73, 79.27)

Corpus

11

34.4

(17.92, 50.83)

Cardia

1

3.1

(0, 9.15)

Fundus

0

0

--

Total

32

Table 9: Caste-wise Assessment of major risk factors

Gurung

Chhetri

Brahmin

Total cases

126

83

60

P

pp value

Data available

for risk factor

93

65

50

Smoked meat

Yes

68

41

18

0.0001**

No

25

24

32

Alcohol

Yes

72

39

19

0.0001**

No

21

26

31

Smoking

Yes

32

25

36

0.0001**

No

61

40

14

** Statistically significant (p value<0.05)

Among all cases in Gurung, Chhetri and Brahmin communities, we could retrieve data on risk factors in 93, 65 and 50 cases respectively. Significant relationship was found between the three risk factors studied and ethnic groups (Table 9). Smoked meat was found to be associated with gastric carcinoma in Gurungs, Chhetris and Brahmins in 73%, 63%, and 36% cases respectively. Similarly alcohol was found to be associated more commonly in Gurungs (77% ) and Chhetris (60%) than among Brahmins (38%) . On the contrary, cases among Brahmins (72%) are found to more associated with smoking than Gurungs (34%) and Chhetris (38%).

Discussion

The gastric carcinoma is one of the most common malignancies worldwide and is among the top five malignancies encountered at Manipal Teaching Hospital 8. Among all the histopathological tissues received in the Dept of Pathology, approximately 5% cases were related to gastric pathology. We have reported a total of 426 cases of gastric malignancy (1.7% of all cases and 35% of all gastric tissue) in the study period. As per our exclusion criteria, 397 cases were included in the study.

Gastric carcinoma is extremely rare before the age of 30 years and most patients are above 50 years3,5. Though a steady decline in the incidence and mortality rates of gastric carcinoma has been observed worldwide over the past several decades, the absolute number of new cases per year is increasing mainly because of the aging of the population11. In our study, majority of the patients (331 cases, 83 %) were in the age range 51 to 70 years. This finding corroborates well with the international trend. However, cases of gastric carcinoma in young and even in children are recorded in world literature and we found 5 cases in the age group of 21-30 years12,13. As seen in other international studies, males are clearly affected more commonly, nearly two times more than females in our data3.

All gastric carcinomas arise from foveolae; in most instances, in a back ground of chronic atrophic gastritis with intestinal metaplasia14,15. The most frequent site of stomach cancer is the distal stomach i.e., the antro-pyloric region3. Carcinomas of the body or the corpus are located mostly along the greater or lesser curvature3,5. In our study also the distal stomach (antrum) is the primary site in 70% of cases followed by the body or corpus (20%).

Grossly, gastric carcinomas show a wide variation5. Dysplasias may present as a flat lesion, difficult to detect on conventional endoscopy3. The gross appearances of advanced carcinoma include flat, ulcerated, or fungating tumor growing into the gastric lumen and deeply invasive tumor growing through the wall of the stomach5,16. Borrmann classified the gross appearance of advanced carcinomas into 4 types based on the proportion of exophytic and endophytic components3,5,17. Fig 1 shows the schematic representation of four gross morphological types described by Borrmann3. Types II and III are common3. Diffuse type (Type IV) spread superficially in the mucosa and submucosa producing flat lesions with or without ulceration. With extensive infiltration, a linitis plastica or leather bottle stomach results. In our study, we analyzed 82 gastrectomy cases. We found type IV (diffuse infiltrating) to be the most common constituting 40% of 82 cases. However, combined type II and III comprise 60%. We did not find any nonulcerated polypoid type ( type I ) in our study. Type IV has been found to be an independent prognostic factor by other studies18. More studies from this country on this aspect are invited. Depending of the relative proportion of mucin and fibrosis, the tumor may have fleshy, fibrous or gelatinous appearance3,5 .

Microscopically, this carcinoma have been divided into two major categories by Lauren in 196519. Lauren classification has been found useful in evaluating the natural history of gastric carcinoma3. According to Lauren Classification, the main two types are "intestinal" and "diffuse" type. Tumors that contain approximately equal quantities of both components are called "mixed" type and carcinomas too undifferentiated to fit into any category are placed in "indeterminate" type3. Intestinal carcinomas form recognizable glands ranging from poorly to moderate and well differentiated. On the other hand, diffuse type consists of poorly cohesive cells diffusely infiltrating the gastric wall with minimal gland formation3,5. This type is currently known as "signet ring" carcinoma as most of the cells contain intracytoplasmic mucin giving the cell the typical signet ring appearance3,5. According the original study by Lauren, intestinal type comprised 53% and diffuse type comprised 33%. In our study, the findings are closely similar with intestinal type being 53% and diffuse type 31%.

H. pylori has been implicated as an etiologic factor in gastric carcinoma through development of chronic gastritis20. Strong evidence has been shown in prospective cohort studies that presence of H. pylori antibodies in serum poses a significant increased risk of carcinoma21. H. pylori causes the sequential steps - chronic gastritis, multifocal atrophy, intestinal metaplasia and intraepithelial neoplasia. Gastritis and atrophy lead to elevated pH altering the colonizing bacterial flora. These bacteria activate reductases that form nitrite from food nitrate. This nitrite reacts with amines, amides and ureas producing carcinogenic N-nitroso compounds22,23. H. pylori however are mainly seen in normal mucosa and are absent in areas with intestinal metaplasia where neoplasia originates3. In our study, we searched for H. pylori in both the neoplastic and nonneoplastic mucosa in all 397 malignant cases. We found presence of H. pylori only in 32 cases (8%). However, it is premature to come to any conclusion and there is scope of further study to assess the association of H. pylori with gastric carcinoma in this part of the world. Among other risk factors, the most consistent association is diet. This is especially true for intestinal carcinoma3. Salt intake, smoked meat, smoked fish, pickled vegetables, chili peppers, alcohol and tobacco are found to incur high risk3, 14. In our study, we classified the incidences of gastric carcinoma in different castes and also tried to find out the importance of smoked meat, alcohol and smoking as risk factors. According to estimation of World Health Organization (WHO), 38.4 % of the total population of Nepal above 15 years of age smoke, of which 48.4% are males and 28.7% are females 25.

Despite a high incidence in many Asian nations, population-based studies indicate that Asian-American patients have improved gastric cancer survival compared with other races and ethnicities26-29. However, the categorization of Asian ethnicities as a single race appears inappropriate, given that Asians are a culturally diverse mix of people that differ widely in country of origin, immigration patterns, socioeconomic status, and lifestyle factors30-32. Nevertheless, epidemiologic studies often aggregate these diverse populations without mention of the specific ethnic subgroups. The flaw in this practice was recently underscored by a report from Kwong et al., who observed wide variations in cancer incidence and mortality among the five most prevalent Asian-American subgroups, namely Korean, Japanese, Chinese, Vietnamese, and Filipino33. These observations highlight the need to carefully examine gastric cancer outcomes among the different Asian ethnicities. In Nepal, we found that Gurungs are more commonly affected followed by Chhetris and Brahmins comprising 32%, 21%, 15% respectively.

Conclusion

Gastric carcinoma is a common malignancy in this part of world. The most high risk group includes elderly males with history of alcoholism & smoked meat from Gurung community and with history of smoking from Brahmin family. Importance of the association of H. pylori in gastric carcinoma among the Nepalese population needs further study, preferably prospective, before any definite conclusion. There is obvious scope of further studies on gastric carcinoma in other parts of this country and also to assess the other risk factors in this population. However we advise that regular endoscopic surveillance should be done at least in the high risk group for the early detection of cancer.

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